KCTD5 regulates Ikaros degradation induced by chemotherapeutic drug etoposide in hematological cells.

Therapy-related leukemia carries a poor prognosis, and leukemia after chemotherapy is a growing risk in clinic, whose mechanism is still not well understood. Ikaros transcription factor is an important regulator in hematopoietic cells development and differentiation. In the absence of Ikaros, lymphoid cell differentiation is blocked at an extremely early stage, and myeloid cell differentiation is also significantly affected. In this work, we showed that chemotherapeutic drug etoposide reduced the protein levels of several isoforms of Ikaros including IK1, IK2 and IK4, but not IK6 or IK7, by accelerating protein degradation, in leukemic cells. To investigate the molecular mechanism of Ikaros degradation induced by etoposide, immunoprecipitation coupled with LC-MS/MS analysis was conducted to identify changes in protein interaction with Ikaros before and after etoposide treatment, which uncovered KCTD5 protein. Our further study demonstrates that KCTD5 is the key stabilizing factor of Ikaros and chemotherapeutic drug etoposide induces Ikaros protein degradation through decreasing the interaction of Ikaros with KCTD5. These results suggest that etoposide may induce leukemic transformation by downregulating Ikaros via KCTD5, and our work may provide insights to attenuate the negative impact of chemotherapy on hematopoiesis.

Dissection of the Pearl of Csaba pedigree identifies key genomic segments related to early ripening in grape.

Pearl of Csaba (PC) is a valuable backbone parent for early-ripening grapevine (Vitis vinifera) breeding, from which many excellent early ripening varieties have been bred. However, the genetic basis of the stable inheritance of its early ripening trait remains largely unknown. Here, the pedigree, consisting of 40 varieties derived from PC, was re-sequenced for an average depth of ∼30×. Combined with the resequencing data of 24 other late-ripening varieties, 5,795,881 high-quality single nucleotide polymorphisms (SNPs) were identified following a strict filtering pipeline. The population genetic analysis showed that these varieties could be distinguished clearly, and the pedigree was characterized by lower nucleotide diversity and stronger linkage disequilibrium than the non-pedigree varieties. The conserved haplotypes (CHs) transmitted in the pedigree were obtained via identity-by-descent analysis. Subsequently, the key genomic segments were identified based on the combination analysis of haplotypes, selective signatures, known ripening-related quantitative trait loci (QTLs), and transcriptomic data. The results demonstrated that varieties with a superior haplotype, H1, significantly (one-way ANOVA, P < 0.001) exhibited early grapevine berry development. Further analyses indicated that H1 encompassed VIT_16s0039g00720 encoding a folate/biopterin transporter protein (VvFBT) with a missense mutation. VvFBT was specifically and highly expressed during grapevine berry development, particularly at veraison. Exogenous folate treatment advanced the veraison of "Kyoho". This work uncovered core haplotypes and genomic segments related to the early ripening trait of PC and provided an important reference for the molecular breeding of early-ripening grapevine varieties.

LncRNA BRCAT54 is downregulated and inhibits cancer cell proliferation by downregulating miR-130b-3p through methylation in prostate cancer.

BRCAT54 and miR-130b-3p are two recently characterized critical players in cancer biology, while their functions in prostate cancer (PC) are unknown. From preliminary sequencing analysis, we observed altered expression of BRCAT54 and miR-130b-3p in PC and an inverse correlation between them. This study was conducted to explore their involvement in PC. A total of 64 PC patients were enrolled to collect paired PC and nontumor tissues. The expression of BRCAT54 and miR-130b-3p were determined by RT-qPCR. Overexpression of BRCAT54 and miR-130b-3p was achieved in PC cells to explore their roles in regulating the expression of each other. Methylation-specific PCR (MSP) was conducted to explore the role of BRCAT54 in regulating promoter methylation of miR-130b-3p. BrdU assay was used to evaluate the role of BRCAT54 and miR-130b-3p in regulating PC cell proliferation. The results showed that PC tissues exhibited downregulation of BRCAT54 and upreglation of miR-130b-3p compared to that in nontumor tissues. They were inversely correlated across PC tissue samples. Overexpression of BRCAT54 decreased RNA accumulation of miR-130b-3p in PC cells. In addition, overexpression of BRCAT54 increased promoter methylation of miR-130b-3p. Moreover, BRCAT54 suppressed the role of miR-130b-3p in promoting PC cell proliferation. In conclusion, BRCAT54 is downregulated in PC and it may inhibit cancer cell proliferation by downregulating miR-130b-3p through methylation.

Puerarin Induces Ferroptosis in Colorectal Cancer Cells via Triggering NCOA4 Upregulation.

Puerarin shows promise as an anti-cancer compound, but its mechanism of action remains unclear. Here we explored whether and how it promotes ferroptosis in a colorectal cancer cell line. The level of ferroptosis and expression of autophagy proteins were compared between puerarin-treated HT-29 cells expressing normal or reduced levels of the autophagy protein ATG5 or the ferritinophagy protein nuclear receptor coactivator 4 (NCOA4). Puerarin increased lipid peroxidation and inhibited cell proliferation in a dose-dependent manner, indicating the induction of ferroptosis. These effects were partially reversed by ferrostatin-1, a scavenger of reactive oxygen species; by the iron chelator deferiprone; by repression of autophagy through administration of 3-methyladenine or knockdown of autophagy-related gene 5 (ATG5); or by repression of ferritinophagy through NCOA4 knockdown. Puerarin may induce the proliferative inhibition of colorectal cancer cells by triggering ferroptosis through a mechanism requiring NCOA4 ferritinophagy.

Status of 18F-PSMA-1007-PET/CT compared with multiparametric MRI in preoperative evaluation of prostate cancer.

PURPOSE: Treatment of primary prostate cancer extremely depends on preoperative stage. The role of 18F-1007-PSMA-PET/CT in preoperative staging has not been well defined. Our aim was to compare the diagnostic performance of 18F-1007-PEMA-PET/CT, mpMRI, and mpMRI + PEMA-PET/CT in local progression and lymph node invasion of prostate cancer using histopathology as the gold standard. MATERIALS AND METHODS: In this retrospective study, all patients with prostate cancer who underwent mpMRI and 18F-PSMA-1007-PET/CT before operation were included. The role of preoperative imaging was evaluated by predicting the sensitivity and specificity of EPE (extraprostatic extension), SVI (seminal vesicle invasion), and lymph node invasion results. RESULTS: Ultimately, 130 patients were included in this study. In the preoperative judgment of EPE and SVI, mpMRI + PSMA-PET/CT had higher sensitivity and specificity. When predicting lymph node metastasis, PSMA-PET/CT was the best choice. The accuracy of mpMRI + PSMA-PET/CT and PSMA-PET/CT in the T and N stages, respectively, was affected by the least factors. CONCLUSIONS: Based on the combined results of mpMRI and 18F-1007-PSMA-PET/CT, the accuracy of the preoperative judgment of prostatic capsule invasion can be improved, which may be conducive to developing intra-fascial technology while ensuring no tumor-touch isolation. PSMA-PET/CT has the advantages over mpMRI alone in terms of lymph node positivity. Compared with PSMA-PET/CT alone, the combined results can improve the sensitivity, but reduce specificity. Therefore, it is recommended to focus on PSMA-PET/CT to decide whether lymph node dissection should be performed.

WNT16 from decidual stromal cells regulates HTR8/SVneo trophoblastic cell function via AKT/beta-catenin pathway.

Decidual stromal cells (DSCs) modulate the function of trophoblasts through various factors. Wnt signaling pathway is active at the maternal-fetal interface. Here, we isolated endometrial stromal cells (ESCs) from women of reproductive ages and DSCs from normal pregnancy during the first trimester (6-10 weeks). Real-time quantitative PCR and western blotting were used to screen out the most variable WNT ligands between ESCs and DSCs, which turned out to be WNT16. Both culture mediums from DSCs and recombinant protein of human WNT16 enhanced the survival and invasion of HTR8/SVneo trophoblastic cells. Furthermore, the regulation of DSCs on trophoblast was partly blockaded after we knocked down WNT16 in DSCs. Treating HTR8/SVneo trophoblastic cells with small molecular inhibitors and small interfering RNA (siRNA), we found that the activity of AKT/beta-catenin (CTNNB1) correlated with the effect of WNT16. The crosstalk of WNT16/AKT/beta-catenin between DSCs and trophoblasts was determined to be downregulated in unexplained recurrent spontaneous abortion. This study suggests that WNT16 from DSCs promotes HTR8/SVneo trophoblastic cells invasion and survival via AKT/beta-catenin pathway at the maternal-fetal interface in human early pregnancy. The disturbance of this crosstalk between DSCs and trophoblasts might cause pregnancy failure.

TORC2/3-mediated DUSP1 upregulation is essential for human decidualization.

Decidualization is the functional transformation process of endometrium in response to ovarian steroids dedicated to support embryo development. Defective decidualization is closely associated with various pregnancy complications such as recurrent miscarriage (RM). Dual specificity MAPK phosphatases (MKPs) are a family of phosphatases specifically regulating mitogen-activated protein kinase (MAPK) signaling with dual specificity for threonine and tyrosine. Here, using RNA-seq,we found that dual specificity phosphatase 1 (DUSP1) expression was prominently elevated among the MKP family members in db-cAMP treated primary human endometrial stromal cells (ESCs). We verified that its induction by db-cAMP in ESCs was in a dose- and time-dependent manner and that primary human decidual stromal cells (DSCs) present higher expression of DUSP1 than ESCs. A protein kinase A (PKA) inhibitor H-89 abolished its induction in ESCs, but not ESI-09, an EPAC1/2 inhibitor. Knock-down of TORC2/3 but not CREB by siRNA in ESCs diminished its induction by db-cAMP. Furthermore, knock-down of DUSP1, as well as TORC2/3 by siRNA caused abnormal activation of JNK during db-cAMP induction in ESCs, accompanied by decreased IGFBP1 expression, an ESC decidualization indicator, which could be fully rescued by a JNK inhibitor SP600125. In addition, Western blot showed that DUSP1 expression was reduced in the DSCs of patients with RM, along with JNK overactivation and decreased IGFBP1 expression. In conclusion, our results demonstrated that TORC2/3-mediated DUSP1 upregulation in response to the cAMP/PKA signaling safeguards IGFBP1 expression via restraining JNK activity, indicating its involvement in ESC decidualization, and that aberrant expression of DUSP1 in DSCs might engage in the pathogenesis of RM.

SERS-based lateral flow immunoassay for sensitive and simultaneous detection of anti-SARS-CoV-2 IgM and IgG antibodies by using gap-enhanced Raman nanotags.

The lateral flow immunoassay (LFIA) has played a crucial role in early diagnosis during the current COVID-19 pandemic owing to its simplicity, speed and affordability for coronavirus antibody detection. However, the sensitivity of the commercially available LFIAs needs to be improved to better prevent the spread of the infection. Here, we developed an ultra-sensitive surface-enhanced Raman scattering-based lateral flow immunoassay (SERS-based LFIA) strip for simultaneous detection of anti-SARS-CoV-2 IgM and IgG by using gap-enhanced Raman nanotags (GERTs). The GERTs with a 1 nm gap between the core and shell were used to produce the "hot spots", which provided about 30-fold enhancement as compared to conventional nanotags. The COVID-19 recombinant antigens were conjugated on GERTs surfaces and replaced the traditional colloidal gold for the Raman sensitive detection of human IgM and IgG. The LODs of IgM and IgG were found to be 1 ng/mL and 0.1 ng/mL (about 100 times decrease was observed as compared to commercially available LFIA strips), respectively. Moreover, under the condition of common nano-surface antigen, precise SERS signals proved the unreliability of quantitation because of the interference effect of IgM on IgG.

Fiber optic evanescent wave humidity sensor based on SiO2/TiO2 bilayer films.

A SiO2/TiO2 bilayer thin-film-based fiber optic humidity sensor was fabricated via a modified dip coating process with enhanced sensitivity. SiO2 film was coated on the surface of the fiber core, followed by deposition of the TiO2 layer on SiO2. The relative humidity (RH) is measured by modulation in intensity of the transmitted laser at room temperature. The optical fiber humidity sensor based on SiO2/TiO2 film shows two-segmented linearity in measurement with sensitivities of 5.35 and 1.94 µW/% RH at 15%-50% RH and 50%-95% RH, respectively. The response time and recovery time are 25 s and 50 s, respectively. To our knowledge, the superior response time and recovery time of the sensor in our study were achieved over those fiber optic humidity sensors reported with modulation in intensity. Furthermore, this fiber optic humidity sensor has a good reproducibility and long-term stability. The sensing mechanism is attributed to effects of moisture on the refractive index and the light absorption coefficient of SiO2 film and modulation in the transmission characteristic of evanescent waves in the optical fiber.

Decidual CD8+T cells exhibit both residency and tolerance signatures modulated by decidual stromal cells.

BACKGROUND: During early pregnancy, tolerance of the semi-allogeneic fetus necessitates comprehensive modifications of the maternal immune system. How decidual CD8+T (CD8+dT) cells balance maternal tolerance of the fetus with defense from invading pathogens remains undefined. METHODS: We investigated the distribution patterns of CD8+T cells and their heterogeneity in paired peripheral blood and decidual tissue in the first trimester of pregnancy using flow cytometry and mRNA-Seq. Gene Set Enrichment Analysis was utilized to determine the transcriptional features of CD8+dT cells. Moreover, we examined activation of T cells when they were cocultured with trophoblasts, in addition to the effect of the fetal-maternal environment on peripheral CD8+T (CD8+pT) cells. RESULTS: We found that, compared with CD8+pT cells, CD8+dT cells consisted mainly of effector memory cells (TEM) and terminally differentiated effector memory cells (TEMRA). Both TEM and TEMRA subsets contained increased numbers of CD27+CD28- cells, which have been shown to possess only partial effector functions. In-depth analysis of the gene-expression profiles of CD8+dT cells revealed significant enrichment in T cell exhaustion-related genes and core tissue residency signature genes that have been found recently to be shared by tissue resident memory cells and tumor-infiltrating lymphocytes (TILs). In accordance with gene expression, protein levels of the exhaustion-related molecules PD-1 and CD39 and the tissue resident molecules CD103 and CXCR3 were increased significantly with almost no perforin secretion in CD8+dT cells compared with CD8+pT cells. However, the levels of granzyme B, IFN-γ, and IL-4 in CD8+dT cells were increased significantly compared with those in CD8+pT cells. Both CD8+dT and CD8+pT cells were not activated after being cocultured with autologous trophoblast cells. Moreover, the production of granzyme B in CD103+CD8+dT cells decreased significantly compared with that in their CD103- counterparts. Coculture with decidual stromal cells and trophoblasts upregulated CD103 expression significantly in CD8+pT cells. CONCLUSIONS: Our findings indicate that the selective silencing of effector functions of resident CD8+dT cells may favor maternal-fetal tolerance and that the decidual microenvironment plays an important role in promoting the residency of CD8+T cells and their tolerance-defense balance.

The role of NMDA receptors in rat propofol self-administration.

BACKGROUND: Propofol is among the most frequently used anesthetic agents, and it has the potential for abuse. The N-methyl-D-aspartate (NMDA) receptors are key mediators neural plasticity, neuronal development, addiction, and neurodegeneration. In the present study, we explored the role of these receptors in the context of rat propofol self-administration. METHODS: Sprague-Dawley Rats were trained to self-administer propofol (1.7 mg/kg/infusion) using a fixed-ratio (FR) schedule over the course of 14 sessions (3 h/day). After training, rats were intraperitoneally administered the non-competitive NDMA receptor antagonist MK-801, followed 10 min later by a propofol self-administration session. RESULTS: After training, rats successfully underwent acquisition of propofol self-administration, as evidenced by a significant and stable rise in the number of active nose-pokes resulting in propofol administration relative to the number of control inactive nose-pokes (P < 0.01). As compared to control rats, rats that had been injected with 0.2 mg/kg MK-801 exhibited a significantly greater number of propofol infusions (F (3, 28) = 4.372, P < 0.01), whereas infusions were comparable in the groups administered 0.1 mg/kg and 0.4 mg/kg of this compound. In addition, MK-801 failed to alter the numbers of active (F (3, 28) = 1.353, P > 0.05) or inactive (F (3, 28) = 0.047, P > 0.05) responses in these study groups. Animals administered 0.4 mg/kg MK-801 exhibited significantly fewer infusions than animals administered 0.2 mg/kg MK-801 (P = 0.006, P < 0.01). In contrast, however, animals in the 0.4 mg/kg MK-801 group displayed a significant reduction in the number of active nose-poke responses (F (3, 20) = 20.8673, P < 0.01) and the number of sucrose pellets (F (3, 20) = 23.77, P < 0.01), while their locomotor activity was increased (F (3, 20) = 22.812, P < 0.01). CONCLUSION: These findings indicate that NMDA receptors may play a role in regulating rat self-administration of propofol.

[Research advances in the function of T cells at the maternal-fetal interface].

Immune tolerance at maternal-fetal interface is the basis for establishment and maintenance of successful pregnancy. T cells are pivotal compositions of uterine decidual immune cells, which are required to mediate anti-infection immunity and protect embryos from external antigens attack. T cells also participate in the complex immune regulation process of maternal acceptance of semi-allogeneic embryos, and play an important role in regulating embryo implantation and maintaining pregnancy. Its dysfunction may lead to early pregnancy failures or mid-late pregnancy complications. This review summarizes the compositions, phenotypic characteristics and functions of decidual T cells at the maternal-fetal interface in recent years, and further describes the regulation of decidual CD4+ and CD8+ T cells in maternal-fetal immune tolerance as well as the molecular mechanisms of abnormal regulation leading to early pregnancy failures. Through the in-depth understanding the mechanism of maternal-fetal immune regulation, it supplies a novel concept on maternal-fetal immune tolerance and new clues for the immunotherapy of pregnancy-related diseases.

microRNA-186 inhibition of PI3K-AKT pathway via SPP1 inhibits chondrocyte apoptosis in mice with osteoarthritis.

Chondrocyte apoptosis has been implicated as a major pathological osteoarthritis (OA) change in humans and experimental animals. We evaluate the ability of miR-186 on chondrocyte apoptosis and proliferation in OA and elucidate the underlying mechanism concerning the regulation of miR-186 in OA. Gene expression microarray analysis was performed to screen differentially expressed messenger RNAs (mRNAs) in OA. To validate the effect of miR-186 on chondrocyte apoptosis, we upregulated or downregulated endogenous miR-186 using mimics or inhibitors. Next, to better understand the regulatory mechanism for miR-186 governing SPP1, we suppressed the endogenous expression of SPP1 by small interfering RNA (siRNA) against SPP1 in chondrocytes. We identified SPP1 is highly expressed in OA according to an mRNA microarray data set GSE82107. After intra-articular injection of papain into mice, the miR-186 is downregulated while the SPP1 is reciprocal, with dysregulated PI3K-AKT pathway in OA cartilages. Intriguingly, miR-186 was shown to increase chondrocyte survival, facilitate cell cycle entry in OA chondrocytes, and inhibit chondrocyte apoptosis in vitro by modulation of pro- and antiapoptotic factors. The determination of luciferase activity suggested that miR-186 negatively targets SPP1. Furthermore, we found that the effect of miR-186 suppression on OA chondrocytes was lost when SPP1 was suppressed by siRNA, suggesting that miR-186 affected chondrocytes by targeting and depleting SPP1, a regulator of PI3K-AKT pathway. Our findings reveal a novel mechanism by which miR-186 inhibits chondrocyte apoptosis in OA by interacting with SPP1 and regulating PI3K-AKT pathway. Restoring miR-186 might be a future therapeutic strategy for OA.

Ultra-smooth TiO2 thin film based optical humidity sensor with a fast response and recovery.

An ultra-smooth $\text{TiO}_2$TiO2 thin film based optical humidity sensor was fabricated via a modified dip coating process. The $\text{TiO}_2$TiO2 film possessed a root mean square roughness of ${2.6 \pm 0.3}\;\text{nm}$2.6±0.3nm. Measurement of relative humidity (RH) was performed by modulation in the intensity of laser transmitted at room temperature. The optical humidity sensor based on $\text{TiO}_2$TiO2 film exhibited two-segmented linearity in the whole RH range. The response time and recovery time were determined to be 27 s and 23 s, respectively. To our knowledge, the optical humidity sensor achieved the fastest recovery to date among those modulated in optical power. The fast response and recovery are attributed to the smooth surface of sensing film, which allows the rapid equilibrium between adsorption and desorption of water molecules on the film surface. In addition, this optical humidity sensor possessed an excellent reproducibility and long-term stability after aging. The sensing mechanism is based on the chemisorption of water molecules in the low RH range and formation of water droplets in the high RH range on the surface of ${\text{TiO}_2}$TiO2 film.

SCM-198 protects endometrial stromal cells from oxidative damage through Bax/Bcl-2 and ERK signaling pathways.

Increasing amounts of evidence demonstrated that accumulative reactive oxygen species (ROS) and apoptosis of human endometrial stromal cells (ESCs) are closely associated with endometrial dysfunction induced by oxidative stress, which plays an important role in the pathological process of multiple gynecological and reproduction-related diseases. SCM-198, an alkaloid active component of Leonurus japonicas Houtt, has been reported to have anti-oxidative activity. However, the specific mechanisms of SCM-198 in the prevention of endometrial damage remain unknown. In the present study, we assessed the effect of SCM-198 on hydrogen peroxide (H2O2)-induced oxidative injury in ESCs. ESCs were pretreated with SCM-198 for 4 h and then challenged with H2O2. Morphology changes, apoptosis rate, and intracellular ROS production were measured to assess the level of oxidative injury. Flow cytometry and western blot analysis were performed to detect the expression levels of Bax, Bcl-2, active-caspase-3, and mitogen-activated protein kinases pathways. Classic inflammation cytokines were measured by real-time polymerase chain reactions. Our results showed that SCM-198 attenuated apoptosis and ROS generation of ESCs induced by H2O2. H2O2 induced the apparent apoptotic characteristics, including fragmentation of DNA, upregulation of Bax/Bcl2, activation of caspase-3, and secretion of inflammation cytokines, which were all ameliorated by SCM-198. Furthermore, H2O2-induced apoptosis-related ERK1/2 pathway activation was restrained by SCM-198 pretreatment. These findings suggested that SCM-198 could protect ESCs from oxidative injury, mainly by inhibiting oxidative stress and reducing apoptosis.

Activation of Rev-erbα attenuates lipopolysaccharide-induced inflammatory reactions in human endometrial stroma cells via suppressing TLR4-regulated NF-κB activation.

Perturbation of the circadian rhythm damages the biological characteristics of cells and leads to their dysfunction. Rev-erbα, an important gene in the transcription-translation loop of circadian rhythm, is involved in regulating the balance between pro-inflammation and anti-inflammation. The disruption of this balance in human endometrial stroma cells (hESCs) destroys their biological behavior function in maintaining the menstrual cycle and embryonic implantation. Whether pharmacological modulation of Rev-erbα affects the inflammation of hESCs remains unclear. In this study, we treated hESCs with lipopolysaccharide (LPS) and found that LPS treatment increased the mRNA levels of pro-inflammatory cytokines, such as interleukin (IL)-1ß, IL-6, IL-8, IL-18, and TNFα, and the secretion of IL-6. SR9009, a Rev-erbα agonist, significantly alleviated the LPS-induced production of pro-inflammatory cytokines in hESCs. Meanwhile, knockdown of Rev-erbα increased the expressions of IL-1ß, IL-6, and IL-8, accompanied by an increased mRNA level of the core clock gene Bmal1. Western blot analysis showed that SR9009 inhibited the expression of toll-like receptor 4 (TLR4) and the activation of NF-κB induced by LPS. All these findings suggested that pharmacological activation of Rev-erbα attenuated the LPS-induced inflammatory response of hESCs by suppressing TLR4-regulated NF-κB activation. This study may provide a strategy for preventing inflammation-related endometrial dysfunction and infertility or recurrent implantation failure.

Layered Chalcogenide Scintillators Enabled by Reversible Hydrous-Induced Phase Transformation for High-Resolution X-ray Imaging.

Scintillation materials have been widely used in various fields, such as medical diagnosis and industrial detection. Chalcogenides have the potential to become a new generation of high-performance scintillation materials due to their high effective atomic number and good resistance to radiation damage. However, research on their application in radiation detection is currently very scarce. Herein, single crystals of rare earth ion-doped ternary chalcogenides NaGaS2/Eu were grown by a high-temperature solid-phase method. It exhibits unique characteristics of structure transformation by absorbing water molecules from the air. To maintain the anhydrous phase of the material, we have used a strategy of organic-inorganic composites of epoxy resin and NaGaS2/Eu to prepare devices for radiation detection and discuss the irradiation luminescence properties of the two phases. The anhydrous phase of NaGaS2/Eu demonstrates excellent sensitivity to X-rays, with a low detection limit of 250 nGy s-1, which is approximately 1/22 of the medical imaging dose. Additionally, composite flexible films were prepared, which exhibited excellent performance in X-ray imaging. These films enable clear observation of a wide range of objects with a high spatial resolution of up to 13.2 line pairs per millimeter (lp mm-1), indicating that chalcogenide holds promising prospects in the realm of X-ray imaging applications.

Causal Relationship Between Circulating Immune Cells and Recurrent Spontaneous Abortion: A Bidirectional Mendelian Randomization Study.

BACKGROUND: Recurrent spontaneous abortion (RSA) is a serious and common complication of pregnancy caused by multiple factors. The etiology remains incompletely understood, but immunologic factors play important roles. Here, we aimed to evaluate whether circulating immune cells causally impacted RSA. METHODS: In this study, we conducted a comprehensive two-sample Mendelian randomization (MR) study to determine the causal association between the 731 immunophenotypes of human peripheral blood lymphocytes and the number of spontaneous abortions as well as recurrent miscarriage. Sensitivity analyses were performed to assess and minimize heterogeneity and horizontal pleiotropy. Reverse MR analysis was used to assess reverse causality. RESULTS: After Bonferroni-correction, eight immunophenotypes were significantly associated with the number of spontaneous abortions: FSC-A on CD4+ T cell (beta = -0.051, 95% CI = [-0.085, -0.017], P-value = 0.004), CD8 on HLA DR+ CD8+ T cell (beta = -0.040, 95% CI = [-0.067, -0.014], P-value = 0.003), HLA DR on CD33dim HLA DR+ CD11b- (beta = -0.021, 95% CI = [-0.036, -0.005], P-value = 0.010), HLA DR+ T cell Absolute Count (beta = 0.022, 95% CI = [0.006, 0.037], P-value = 0.008), HLA DR+ T cell % lymphocyte (beta = 0.026, 95% CI = [0.010, 0.041], P-value = 0.001), HLA DR+ T cell % T cell (beta = 0.023, 95% CI = [0.007, 0.039], P-value = 0.004), HLA DR+ CD4+ T cell % lymphocyte (beta = 0.034, 95% CI = [0.007, 0.060], P-value = 0.012), and HLA DR on B cell (beta = 0.012, 95% CI = [0.003, 0.021], P-value = 0.010). In addition, we identified two immunophenotypes associated with recurrent miscarriage: HLA DR on B cell (OR = 0.854, 95% CI = [0.757, 0.964], P-value = 0.011), and CD19 on naive-mature B cell (OR = 4.595, 95% CI = [1.674, 12.617], P-value = 0.003). There was no evidence of heterogeneity, horizontal pleiotropy and reverse causality. CONCLUSIONS: Our study demonstrated a tight link between adaptive immune cells and RSA through genetic means, thus providing potential therapeutic targets or novel diagnostic biomarkers.

Cytochrome P450 CYP736A12 is crucial for Trichoderma asperellum-induced alleviation of phoxim phytotoxicity and reduction of pesticide residue in tomato roots.

Trichoderma can enhance the metabolism of organophosphate pesticides in plants, but the mechanism is unclear. Here, we performed high-throughput transcriptome sequencing of roots upon Trichoderma asperellum (TM) inoculation and phoxim (P) application in tomato (Solanum lycopersicum L.). A total of 4059 differentially expressed genes (DEGs) were obtained, including 2110 up-regulated and 1949 down-regulated DEGs in P vs TM+P. COG and KOG analysis indicated that DEGs were mainly enriched in signal transduction mechanisms. We then focused on the pesticide detoxification pathway and screened out cytochrome P450 CYP736A12 as a putative gene for functional analysis. We suppressed the expression of CYP736A12 in tomato plants by virus-induced gene silencing and analyzed tissue-specific phoxim residues, oxidative stress markers, glutathione pool, GST activity and related gene expression. Silencing CYP736A12 significantly increased phoxim residue and induced oxidative stress in tomato plants, by attenuating the TM-induced increased activity of antioxidant and detoxification enzymes, redox homeostasis and transcripts of detoxification genes including CYP724B2, GSH1, GSH2, GR, GPX, GST1, GST2, GST3, and ABC. The study revealed a critical mechanism by which TM promotes the metabolism of phoxim in tomato roots, which can be useful for further understanding the Trichoderma-induced xenobiotic detoxification and improving food safety.